Triethylamine → (R)-1'-[2-(1-Butyryloxy-ethyl)-pyrimidin-4-yl]-6-chloro-spiro[chroman-2,4'-piperidin]-4-one

HRID 394514Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 394514
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:15](=[CH:16][CH:17]=1)[O:14][C:8]1([CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[CH2:7][C:6]2=[O:18].[C:19]([O:24][C@@H:25]([C:27]1[N:32]=[C:31](Cl)[CH:30]=[CH:29][N:28]=1)[CH3:26])(=[O:23])[CH2:20][CH2:21][CH3:22].C(N(CC)CC)C>C(O)(C)C>[C:19]([O:24][C@@H:25]([C:27]1[N:28]=[C:29]([N:11]2[CH2:12][CH2:13][C:8]3([CH2:7][C:6](=[O:18])[C:5]4[C:15](=[CH:16][CH:17]=[C:3]([Cl:2])[CH:4]=4)[O:14]3)[CH2:9][CH2:10]2)[CH:30]=[CH:31][N:32]=1)[CH3:26])(=[O:23])[CH2:20][CH2:21][CH3:22]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 10944226(R)-1-(4-chloro-pyrimidin-2-yl)ethyl butyrateHCID 223286586-Chlorospiro[chroman-2,4'-piperidin]-4-one hydrochloride

Produkt 1

HCID 54550021(R)-1'-[2-(1-Butyryloxy-ethyl)-pyrimidin-4-yl]-6-chloro-spiro[chroman-2,4'-piperidin]-4-oneAusbeute 100 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Versuchsvorschrift

To a solution of 6-chloro-spiro[chroman-2,4′-piperidin]-4-one hydrochloride (prepared according to the method of Example 78, Step A, 175 mg, 0.61 mmol) in isopropanol (5 mL) was added (R)-1-(4-chloro-pyrimidin-2-yl)-ethyl butyrate (prepared according to the method of Preparation Seven, 160 mg, 0.70 mmol) followed by triethylamine (0.29 mL, 2.1 mmol). This mixture was stirred at reflux for 1.5 h, concentrated, and purified by flash column chromatography (1% methanol/chloroform) to give 270 mg (100%) of the title compound of Example 78, Step B as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 8.19 (d, 1H), 7.83 (d, 1H), 7.44 (dd, 1H), 6.97 (d, 1H), 6.37 (d, 1H), 5.64 (q, 1H), 4.18 (app s, 2H), 3.34 (t, 2H), 2.72 (s, 2H), 2.37 (t, 2H), 2.10 (d, 2H), 1.71-1.60 (c, 4H), 1.55 (d, 3H), 0.94 (t, 3H); MS (APCI) 444, 446 (MH+).

Aufarbeitung

  1. customprepared
  2. customaccording to the method of Preparation Seven, 160 mg, 0.70 mmol)
  3. temperatureat reflux for 1.5 h
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (1% methanol/chloroform)

Quellen und Nachweise

ORD-Eintrag
ord-468f3cb68d804616893ac760d47c9a20
Quelldatensatz
uspto-grants-2003_08
Patentnummer
US06602875B2

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